Daratumumab combined with teclistamab or talquetamab for frail adults with newly diagnosed multiple myeloma

Is this trial a fit for you?

A plain-English reading of the study's rules. Only the study team can confirm whether you qualify.

What this trial studies

This is a multicenter, open-label phase II study with two parallel cohorts enrolling frail, treatment-naïve adults with measurable newly diagnosed multiple myeloma. One cohort receives teclistamab plus daratumumab and the other receives talquetamab plus daratumumab for a fixed initial treatment period. After a treatment-free interval, patients with confirmed disease progression may be re-treated with the same assigned combination. The primary outcome is progression-free survival at 18 months, with follow-up during a post-treatment phase.

Why it matters

Who can join: the full rules

Inclusion Criteria:

1. Patient is ≥18 years of age and capable of giving informed consent and must sign an informed consent form (ICF), indicating that they understand the purpose of, and procedures required for, the study and is willing to participate in the study
2. Newly diagnosed and treatment-naïve patients with a confirmed diagnosis of MM with measurable disease according to IMWG criteria
3. Measurable disease defined as M-protein in the serum (≥1 g/dL) or serum free light chain assay ≥10 mg/dL \[≥100 mg/L\] and abnormal serum immunoglobulin kappa/lambda FLC ratio
4. Frail according to the Simplified IMWG frailty index
5. Have clinical laboratory values meeting defined range
6. Patients of childbearing potential must agree to use adequate/highly effective contraception from the time of signing the informed consent form through 3 months after the last dose of study drug

Exclusion Criteria:

1. Non-secretory MM or measurable disease by urine or plasmacytoma only
2. Central nervous system involvement of myeloma
3. Significant pulmonary dysfunction
4. Stroke, transient ischemic attack, or seizure within 6 months of eligibility
5. Evidence of active systemic viral, fungal, or bacterial infections, requiring systemic antimicrobial therapy
6. HIV and Hepatitis infections
7. Exclude for any of the following:

   1. Any history of malignancy other than MM which is considered at high risk of recurrence requiring treatment or a malignancy that has been treated with chemotherapy currently affecting bone marrow capacity.
   2. Any active malignancy (ie, progressing or requiring treatment change in the last 24 months) other than multiple myeloma.
8. Active autoimmune disease requiring systemic immunosuppressive therapy within 6 months before eligibility
9. Contraindications or life-threatening allergies, hypersensitivity, or intolerance to any study treatment or its excipients (refer to IB and most recently applicable RSI)
10. Extensive radiotherapy within 14 days or focal radiation only within 7 days of eligibility
11. Current or active therapy for multiple myeloma or received a cumulative dose corticosteroids equivalent to \>40 mg dexamethasone within the 14 days prior to C1D1
12. Received a live attenuated vaccine ≤4 weeks before eligibility. Non-live vaccines or non-replicating authorized for emergency use (eg, COVID-19) are allowed
13. Received a strong CYP3A4 inducer or use of St. John's wort ≤5 half-lives prior to dosing
14. Patient had major surgery or significant traumatic injury within 2 weeks prior to eligibility. Kyphoplasty or Vertebroplasty is not considered major surgery
15. Have received an investigational drug (including investigation vaccines) or used an invasive investigational medical device \<4 week or 5 PK half-lives, before eligibility or is currently enrolled in an interventional investigational study except if only long-term survival data are collected
16. Concurrent medical or psychiatric condition or disease (eg, uncontrolled diabetes, alcohol or drug abuse, severe dementia or altered mental status), that is likely to interfere with study procedures or results, or that in the opinion of the investigator would constitute a hazard for participation in the study
17. Any other issue that would impair the ability of the patient to receive or tolerate the planned treatment at the investigational site, to understand informed consent or any condition for which, in the opinion of the investigator, participation would not be in the best interest of the patient (eg,, compromise the well-being) or that could prevent, limit, or confound the protocol-specified assessments

Where it's running

• IT-Ascoli Piceno-Ospedale Mazzoni [01-016]
  Ascoli Piceno, Italy Recruiting
• IT-Como-Ospedale Classificato Valduce [01-104]
  Como, Italy Recruiting
• IT-Milano-Ospedale S. Carlo Borromeo [01-105]
  Milan, Italy Recruiting
• IT-Novara-A.O.U. Maggiore della Carità [01-010]
  Novara, Italy Recruiting
• IT-Pescara-Azienda USL di Pescara P.O. dello Spirito Santo [01-053]
  Pescara, Italy Recruiting
• ES-Murcia-H.U. Virgen de la Arrixaca [06-016]
  Murcia, Spain Recruiting

Study contacts

• Principal investigator: Sonja Zweegman — Vrije Universiteit Medical Center (VUMC)
• Study coordinator: Clinical Trial Office
• Email: amministrazione@emnresearch.it
• Phone: +390110243236

Similar studies

Other studies for the same condition or treatment. Recruiting studies are listed first.

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• Combining teclistamab and talquetamab with daratumumab and lenalidomide for newly diagnosed multiple myeloma

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  This phase 2 trial tests whether infliximab can prevent cytokine release syndrome in patients with relapsed or refractory multiple myeloma who are being treated with teclistamab or talquetamab.

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• Tec Dara for newly diagnosed multiple myeloma with light chain amyloidosis

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• Teclistamab plus daratumumab for newly diagnosed AL amyloidosis

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• Daratumumab‑hyaluronidase plus teclistamab vs standard daratumumab combinations for high‑risk relapsed or refractory multiple myeloma

  This phase 2 trial tests whether combining daratumumab with teclistamab helps people with high‑risk myeloma that has not responded to treatment or has come back, compared to usual daratumumab‑based therapies.

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How to take part

1. Review the eligibility criteria above with your treating physician.
2. Check the official listing on ClinicalTrials.gov for the latest contact details and recruitment status.
3. Contact the study coordinator or principal investigator to ask for pre-screening. Pre-screening is free and never obligates you to enroll.